Alterations in cardiac SR Ca(2+)-release channels during development of heart failure in cardiomyopathic hamsters.
The cardiomyopathic Syrian hamster develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, cardiac dilatation, and congestive heart failure. This study aimed to identify alterations in cardiac mechanical function and in the cellular content of sarcoplasmic reticulum (SR) Ca(2+)-release channels (ryanodine receptors, RyR) in the heart of the UM-X7.1 cardiomyopathic hamster during the development of heart failure. Experimental and healthy control hamsters were examined at 8, 18, and 28 wk of age. The UM-X7.1 hamsters had developed left ventricular (LV) hypertrophy at 8 wk and a marked LV dilatation at 18-28 wk. During the latter stage, the UM-X7.1 hamster hearts showed global hypokinesis. Equilibrium binding assays of high-affinity sites for [3H]ryanodine were performed in ventricular homogenate preparations. There was no significant difference between the two groups in the maximum number of [3H]ryanodine binding sites (Bmax) at either 8 or 18 wk of age, although the cardiac pump function was impaired in UM-X7.1 hamsters at 18 wk of age. By 28 wk, Bmax was significantly lower in the UM-X7.1 hamsters. Quantitative immunoblot assay revealed that the content of RyR protein in cardiomyopathic hearts, which was increased at the early stage, declined to below normal as heart failure advanced. These results suggest that the number of RyR in the UM-X7.1 cardiomyopathic hamsters was preserved at both the hypertrophic and early stages of heart failure with a possibly compensatory increase in the level of protein expression, although the cardiac function already showed a tendency to be impaired.
Ueyama
T
T
Second Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
Ohkusa
T
T
Hisamatsu
Y
Y
Nakamura
Y
Y
Yamamoto
T
T
Yano
M
M
Matsuzaki
M
M
D000375:Aging; D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006224:Cricetinae; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000254:growth & development / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine